miR-302b maintains "stemness" of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression.
Embryonic stem cells (ESCs) and embryonal carcinoma cells (ECCs) possess the remarkable property of self-renewal and differentiation potency. They are model preparations for investigating the underlying mechanisms of "stemness". microRNAs are recently discovered small noncoding RNAs with a broad spectrum of functions, especially in control of development. Here, we show that miR-302b indirectly regulates expression of the pluripotent stem cell marker Oct4, and it directly regulates expression of Cyclin D2 protein, a developmental regulator during gastrulation. Using loss-of function and gain-of function approaches, we demonstrate that functional miR-302b is necessary to maintain stem cell self-renewal and inhibit neuronal differentiation of human ECCs. During retinoic acid-induced neuronal differentiation, Cyclin D2 protein but not mRNA expression is strongly increased, concurrent with the down-regulation of miR-302b and Oct4. Our results suggest that miR-302b plays an important role in maintaining the pluripotency of ECCs and probably ESCs, by post-transcriptional regulation of Cyclin D2 expression.
Lee
Nan Sook
NS
Division of Molecular Medicine, Beckman research Institute of the City of Hope, Duarte, CA, USA.
Kim
Jong Soo
JS
Department of Anatomy and Cell Biology and Department of Biomedical Science, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Cho
Wha Ja
WJ
Department of Anatomy and Cell Biology and Department of Biomedical Science, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Lee
Man Ryul
MR
Department of Anatomy and Cell Biology and Department of Biomedical Science, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Steiner
Riley
R
Department of Biology and Department of Diplomacy and World Affairs, Occidental College, CA, USA.
Gompers
Andrea
A
Department of Biological Sciences, Califonia State University, Los Angeles, CA, USA.
Ling
Daijun
D
Division of Neuroscience, Beckman research Institute of the City of Hope, Duarte, CA, USA.
Zhang
Jae
J
Division of Neuroscience, Beckman research Institute of the City of Hope, Duarte, CA, USA.
Strom
Pl
P
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Behlke
Mark
M
Integrated DNA Technologies, Inc., Coralville, IA, USA.
Moon
Sung-Hwan
SH
CHA Stem Cell Institute & CHA Biotech, Pochon CHA University, Seoul, Republic of Korea.
Salvaterra
Paul M
PM
Division of Neuroscience, Beckman research Institute of the City of Hope, Duarte, CA, USA.
Jove
Richard
R
Division of Molecular Medicine, Beckman research Institute of the City of Hope, Duarte, CA, USA.
Kim
Kye-Seong
KS
Department of Anatomy and Cell Biology and Department of Biomedical Science, College of Medicine, Hanyang University, Seoul, Republic of Korea. Electronic address: ks66kim@hanyang.ac.kr.
D002454:Cell Differentiation; D045744:Cell Line, Tumor; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation
C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger